Electrostatic potential derived charges for enzyme cofactors: methods, correlations, and scaling for organic...

The correlations between electrostatic potential (ESP) derived atomic charges for a wide range of different quantum mechanical approaches and basis sets have been investigated for both small and large organic structures including several enzyme cofactors. The previously observed linear correlation between ESP charges calculated by different approaches has been verified to extend to many different basis sets and procedures including effective core potential (ECP) basis sets, density functional theory (DFT) approaches, a hybrid Hartree-Fock (HF)/DFT approach, and inclusion of electron correlation corrections. Above a threshold level of complexity, most procedures and basis sets give results that correlate very well (linear correlation coefficients > 0.99), including several procedures that have reasonable computational costs for large molecules. These procedures have been used to calculate ESP charges for five different types and forms of enzyme cofactors: biotin, pyridoxal-5'-phosphate, pyridoxamine-5'-phosphate, and the flavin mononucleotide in two different oxidation states.